The development of drugs for eye disorders is a growing field with the market for therapies targeting retinal disorders expected to grow to $14.8 billion by 2022. There are no adequate in vitro models that recapitulate the complex structure of the mature human retina, therefore, the majority of efficacy and safety testing in opthalmological drug development is performed in animals (rodents and rabbits). Investigating the ocular safety of new compounds requires at least 20 animals per compound.

To solve this Challenge, the winning team led by Professor Lyle Armstrong from Newcells Biotech Ltd will use human induced pluripotent stem cells (hiPSC) to create 3D retinal organoids that more closely recapitulate the structure and function of the human retina, which can be used for large scale disease modelling, toxicology and pharmacology screening to replace the use of animals in the discovery of new ophthalmic drugs.

In Phase 1, the team generated 3D laminated human retinae containing all of the major cell types that formed functional synapses, responded to light and electrophysiological stimuli, and accurately identified two compounds known to be toxic to the human retina. In Phase 2, the model will be developed further through incorporating microglia and adaption to rodent and primate derived iPSC, optimising the cryopreservation process to ensure the organoids are accessible worldwide and extending the compound screen to validate the model as a tool for efficacy and toxicity screening.

Full details about this CRACK IT Challenge can be found on the CRACK IT website.